Multimodal management of giant solid hemangioblastomas in two patients with preoperative embolization.

Background: Hemangioblastomas are benign vascular neoplasms, World Health Organization grade I, with the most frequent location in the cerebellum. Complete microsurgical resection can be a challenge due to excessive bleeding, which is why preoperative embolization takes importance. Case Description: Two clinical cases are presented, a 25-year-old woman and a 75-year-old man, who presented with intracranial hypertension symptoms due to obstructive hydrocephalus; a ventriculoperitoneal shunt was placed in both cases; in addition, they presented with cerebellar signs. Both underwent embolization with ethylene vinyl alcohol copolymer, with blood flow reduction. After that, they underwent microsurgical resection within the 1st-week post embolization, obtaining, in both cases, gross total resection without hemodynamic complications, with clinical improvement and good surgical outcome. It is worth mentioning that surgical management is the gold standard that allows a suitable surgical approach, like in our patients, for which a lateral suboccipital craniotomy was performed. Conclusion: Solid hemangioblastomas are less frequent than their cystic counterparts. The treatment is the surgical resection, which is a challenge and always has to be considered as an arteriovenous malformation in the surgical planning, including preoperative embolization to reduce perioperative morbidity and mortality and get good outcomes.

The exonuclease TREX1 constitutes an innate immune checkpoint limiting cGAS/STING-mediated antitumor immunity.

The DNA exonuclease TREX1 (Three-prime repair exonuclease 1) is critical for preventing autoimmunity in mice and humans by degrading endogenous cytosolic DNA, which otherwise triggers activation of the innate cGAS/STING pathway leading to the production of type I IFNs. Since tumor cells are prone to aberrant cytosolic DNA accumulation, we hypothesized that they are critically dependent on TREX1 activity to limit their immunogenicity. Here we show, that in tumor cells TREX1 indeed restricts the spontaneous activation of the cGAS/STING pathway and the subsequent induction of a type I IFN response. As a result, TREX1 deficiency compromised in vivo tumor growth in mice. This delay depended on a functional immune system, systemic type I IFN signaling, and tumor-intrinsic cGAS expression. Mechanistically, we show that tumor TREX1 loss drove activation of CD8 T cells and NK cells, prevented CD8 T cell exhaustion, and remodeled an immunosuppressive myeloid compartment. Consequently, TREX1 deficiency synergized with T cell-directed immune checkpoint blockade. Collectively, we conclude that TREX1 is essential to limit tumor immunogenicity, and that targeting this innate immune checkpoint remodels the tumor microenvironment and enhances anti-tumor immunity by itself and in combination with T cell-targeted therapies.

Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells.

Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. However, there remains little consensus on the mechanism(s) of response with this combination2. Here we find that a high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation is associated with a clinical benefit in patients who received the combination treatment. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development.

Microscopic in-situ analysis of the mucosal healing around implants treated by protease activated receptor 4-agonist peptide or perpendicularly protruded type I collagen in rats.

Enhanced mucosal sealing around titanium implants can reduce complications such as peri-implantitis. The present study aims to investigate the mucosal healing at the early stage around the protease activated receptor 4-agonist peptide (PAR4-AP)- or perpendicularly protruded type I collagen (pCol)-treated titanium implants. A total of 72 implants were placed in 36 rats in the study. Following extractions, two tissue-level implants among the following three different surfaces, PAR4-AP-coated (PAR4 group, n = 24), pCol-treated (pCol group, n = 24) and non-treated (control group, n = 24) ones, were placed in the maxillae of each rat based on a split-mouth design. The specimens retrieved at 8 h (n = 8 per group), 3 days (n = 8 per group), and 2 weeks (n = 8 per group), were immunostained and tissue-cleared, and the signals of laminin-5 and collagen fibers were observed under multiphoton microscopy. Statistical analyses were performed using linear mixed model with post hoc tests to compare differences between the groups. While there was no intergroup difference at 8 h, the laminin-5 at 3 days was more abundant near the PAR4-group-surface, and its area was significantly larger in the PAR4 group (0.0204 ± 0.0194 mm2 ) than the control (0.0019 ± 0.0025 mm2 , p = .001) and pCol (0.0023 ± 0.0022 mm2 , p < .001) groups. The pCol group showed a significantly larger area of collagen fibers (0.0230 ± 0.0148 mm2 ) compared to the control (0.0035 ± 0.0051 mm2 , p = .002) and PAR4 (0.0031 ± 0.0057 mm2 , p < .001) groups at 3 days. At 3 days and 2 weeks, the collagen fiber orientation of the pCol group showed a more perpendicular manner compared to the control and PAR4 groups. The signal of basal lamina and collagen fibers were stronger around the PAR4-AP- and pCol-treated titanium surfaces, respectively during the early healing stage. This could have implications for improved mucosal sealing around dental implants, potentially reducing complications such as peri-implantitis.

Condições de trabalho, adoecimento e enfrentamento da enfermagem na pandemia de covid-19 em uma capital brasileira / Working conditions, illness and nursing coping in the covid-19 pandemic in a brazilian capital / Condiciones de trabajo, enfermedades y enfermería enfrentando la pandemia del covid-19 en una capital brasileña

Objetivo: Descrever as condições de trabalho, adoecimento e o enfrentamento da enfermagem na pandemia de COVID-19 em uma capital brasileira. Métodos: Trata-se de um estudo descritivo, transversal, com abordagem quantitativa. Os dados foram coletados entre agosto e setembro de 2021, de forma on-line. A análise foi realizada por meio do BioEstat 5.0, com técnicas de estatística descritiva e analítica a partir do teste Qui-quadrado de Pearson e do Exato de Fisher, sendo calculado o Odds Ratio nas variáveis em que houve associação significativa. Resultados: Dos 121 participantes do estudo, 106 eram do sexo feminino e mais de 50% possuíam dois vínculos de trabalho. 102 profissionais referiram receber baixos salários pela complexidade do trabalho desenvolvido e 46 apontaram condições precárias para o exercício profissional. Foi encontrada associação estatística na variável referente às orientações de como inspecionar as máscaras N95/PFF2 ou equivalente (p=0.017; OR=0.31; IC 95%=0.13-0.77) e na variável acerca dos profissionais que já apresentaram sintomas de COVID-19 e/ou tiveram diagnóstico confirmado (p=0.047; OR=0.43; IC 95%=0.20-0.93). Conclusão: O presente estudo aponta a necessidade de melhor organização e condições de trabalho nos serviços de saúde de forma que os profissionais de enfermagem possam prestar uma assistência de qualidade. (AU)

Objective: To describe the working conditions, illness and nursing coping in the COVID-19 pandemic in a Brazilian capital. Methods: This is a descriptive, cross-sectional study with a quantitative approach. Data were collected between August and September 2021, online. The analysis was performed using BioEstat 5.0, with descriptive and analytical statistical techniques from Pearson's chi-square test and Fisher's exact test, with the Odds Ratio being adequate for the variables in which there was a linked association. Results: Of the 121 study participants, 106 were female and more than 50% had two jobs. 102 professionals reported salaries earned due to the complexity of the work performed and 46 indicated precarious conditions for professional practice. A statistical association was found regarding the guidelines on how to inspect with masks N95 / PFF2 or equivalent (p = 0.017; OR = 0.31; 95% CI = 0.13-0.77) and the relative variable of professionals who are already associated students of COVID-19 and/or had a confirmed diagnosis (p = 0.047; OR = 0.43; 95% CI = 0.20-0.93). Conclusion: This study points to the need for better organization and working conditions in health services so that nursing professionals must provide quality care. (AU)

Objetivo: Describir las condiciones de trabajo, enfermedad y afrontamiento de enfermería en la pandemia de COVID-19 en una capital brasileña. Métodos: Se trata de un estudio descriptivo, transversal con enfoque cuantitativo. Los datos se recopilaron entre agosto y septiembre de 2021, en línea. El análisis se realizó mediante BioEstat 5.0, con técnicas estadísticas descriptivas y analíticas de la prueba chi-cuadrado de Pearson y la prueba exacta de Fisher, siendo la Odds Ratio adecuada para las variables en las que existía asociación ligada. Resultados: De los 121 participantes del estudio, 106 eran mujeres y más del 50% tenían dos trabajos. 102 profesionales reportaron sueldos percibidos por la complejidad del trabajo realizado y 46 señalaron condiciones precarias para el ejercicio profesional. Se encontró asociación estadística con respecto a las guías sobre cómo inspeccionar con mascarilla N95 / PFF2 o equivalente (p = 0.017; OR = 0.31; IC 95% = 0.13-0.77) y la variable relativa de profesionales que ya son estudiantes asociados de COVID- 19 y / o tenían un diagnóstico confirmado (p = 0,047; OR = 0,43; IC 95% = 0,20-0,93). Conclusión: Este estudio apunta a la necesidad de una mejor organización y condiciones de trabajo en los servicios de salud para que los profesionales de enfermería deban brindar una atención de calidad. (AU)

Activation of Angiopoietin-Tie2 Signaling Protects the Kidney from Ischemic Injury by Modulation of Endothelial-Specific Pathways.

SIGNIFICANCE STATEMENT: Ischemia-reperfusion AKI (IR-AKI) is common and causes significant morbidity. Effective treatments are lacking. However, preclinical studies suggest that inhibition of angiopoietin-Tie2 vascular signaling promotes injury, whereas activation of Tie2 is protective. We show that kidney ischemia leads to increased levels of the endothelial-specific phosphatase vascular endothelial protein tyrosine phosphatase (VE-PTP; PTPRB), which inactivates Tie2. Activation of Tie2 through VE-PTP deletion, or delivery of a novel angiopoietin mimetic (Hepta-ANG1), abrogated IR-AKI in mice. Single-cell RNAseq analysis showed Tie2 activation promotes increased Entpd1 expression, downregulation of FOXO1 target genes in the kidney vasculature, and emergence of a new subpopulation of glomerular endothelial cells. Our data provide a molecular basis and identify a candidate therapeutic to improve endothelial integrity and kidney function after IR-AKI. BACKGROUND: Ischemia-reperfusion AKI (IR-AKI) is estimated to affect 2%-7% of all hospitalized patients. The significant morbidity and mortality associated with AKI indicates urgent need for effective treatments. Previous studies have shown activation of the vascular angiopoietin-Tie2 tyrosine kinase signaling pathway abrogates ischemia-reperfusion injury (IRI). We extended previous studies to (1) determine the molecular mechanism(s) underlying kidney injury and protection related to decreased or increased activation of Tie2, respectively, and (2) to test the hypothesis that deletion of the Tie2 inhibitory phosphatase vascular endothelial protein tyrosine phosphatase (VE-PTP) or injection of a new angiopoietin mimetic protects the kidney from IRI by common molecular mechanism(s). METHODS: Bilateral IR-AKI was performed in VE-PTP wild-type or knockout mice and in C57BL/6J mice treated with Hepta-ANG1 or vehicle. Histologic, immunostaining, and single-cell RNA sequencing analyses were performed. RESULTS: The phosphatase VE-PTP, which negatively regulates the angiopoietin-Tie2 pathway, was upregulated in kidney endothelial cells after IRI, and genetic deletion of VE-PTP in mice protected the kidney from IR-AKI. Injection of Hepta-ANG1 potently activated Tie2 and protected the mouse kidney from IRI. Single-cell RNAseq analysis of kidneys from Hepta-ANG1-treated and vehicle-treated mice identified endothelial-specific gene signatures and emergence of a new glomerular endothelial subpopulation associated with improved kidney function. Overlap was found between endothelial-specific genes upregulated by Hepta-ANG1 treatment and those downregulated in HUVECs with constitutive FOXO1 activation, including Entpd1 / ENTPD1 that modulates purinergic receptor signaling. CONCLUSIONS: Our data support a key role of the endothelium in the development of IR-AKI, introduce Hepta-ANG1 as a putative new therapeutic biologic, and report a model to explain how IRI reduces Tie2 signaling and how Tie2 activation protects the kidney. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_05_23_JSN_Ang_EP23_052323.mp3.

Anti-AMPA Receptor Autoantibodies Reduce Excitatory Currents in Rat Hippocampal Neurons.

The GluR3 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) has been identified as a target for autoantibodies (Aabs) in autoimmune encephalopathy and other diseases. Recent studies have proposed mechanisms by which these Aabs act, but their exact role in neuronal excitability is yet to be established. Patient Aabs have been shown to bind to specific regions within the GluR3 subunit. GLUR3B peptides were designed based on described (ELISA) immunogenic epitopes for Aabs and an immunisation strategy was used to generate novel anti-AMPAR Aabs. Target-specific binding and specificity of affinity-purified anti-AMPAR Aabs was confirmed using enzyme-linked immunosorbent assay, immunocytochemistry and Western blot. Functional anti-AMPAR Aab effects were determined on excitatory postsynaptic currents (EPSCs) from primary hippocampal neurons using whole-cell patch-clamp electrophysiology. Acute (10 or 30 min) or longer-term (24 h) application of anti-AMPAR Aabs caused a significant reduction in the mean frequency of spontaneous and miniature EPSCs in hippocampal neurons. Our data demonstrate that anti-AMPAR Aabs targeting peptides linked to auto-immune diseases mediate inhibitory effects on neuronal excitability at the synaptic level, such effects may lead to disruption of the excitatory/inhibitory balance at a network level.

Successful long-term management of metastatic clear cell renal cell carcinoma with nivolumab: a case report and literature review.

In Colombia, renal cancer is a rare condition, with clear cell renal cell carcinoma (ccRCC) being the most prevalent neoplasm. In recent years, immune checkpoint inhibitors (ICI) have been proposed for the management of metastatic disease, as they have shown improved rates of response and long-term survival. Furthermore, they exhibit a favourable tolerance profile, and adverse events causing significant morbidity are infrequent. We report the case of a 61-year-old male patient initially diagnosed with early-stage ccRCC who underwent right nephrectomy in 2009. Six years later, disease recurrence with metastatic compromise was documented, which led to the resection of the L1 vertebral body followed by radiotherapy and maintenance treatment with sunitinib. Due to disease progression, treatment with sunitinib was discontinued. Subsequently, everolimus was initiated as second-line immunotherapy, which was later discontinued due to the appearance of new metastatic lesions. In 2017, the patient was referred to our institution, where a third-line pharmacological treatment with nivolumab was initiated. In 2022, complete remission by positron emission tomography-computed tomography (PET-CT) was evidenced, which has been sustained to date. This case demonstrates the efficacy and safety of ICI in patients with metastatic ccRCC. The case presented is relevant in that it describes the achievement of complete remission in a patient who did not respond to the first two lines of immunotherapy. Given the limited literature regarding the discontinuation of therapy after achieving sustained remission, further research is warranted to explore this topic.

CD1a promotes systemic manifestations of skin inflammation.

Inflammatory skin conditions are increasingly recognised as being associated with systemic inflammation. The mechanisms connecting the cutaneous and systemic disease are not well understood. CD1a is a virtually monomorphic major histocompatibility complex (MHC) class I-like molecule, highly expressed by skin and mucosal Langerhans cells, and presents lipid antigens to T-cells. Here we show an important role for CD1a in linking cutaneous and systemic inflammation in two experimental disease models. In human CD1a transgenic mice, the toll-like receptor (TLR)7 agonist imiquimod induces more pronounced splenomegaly, expansion of the peripheral blood and spleen T cell compartments, and enhanced neutrophil and eosinophil responses compared to the wild-type, accompanied by elevated skin and plasma cytokine levels, including IL-23, IL-1α, IL-1ß, MCP-1 and IL-17A. Similar systemic escalation is shown in MC903-induced skin inflammation. The exacerbated inflammation could be counter-acted by CD1a-blocking antibodies, developed and screened in our laboratories. The beneficial effect is epitope dependent, and we further characterise the five best-performing antibodies for their capacity to modulate CD1a-expressing cells and ameliorate CD1a-dependent systemic inflammatory responses. In summary, we show that a therapeutically targetable CD1a-dependent pathway may play a role in the systemic spread of cutaneous inflammation.

Caminhos percorridos pelos futuros enfermeiros para formação complementar em saúde mental / Paths taken by future nurses for supplementary training in mental health

Objetivo: Descrever os caminhos percorridos pelos futuros enfermeiros na busca por complementar a formação em saúde mental. Métodos: Estudo descritivo-exploratório, com abordagem qualitativa, realizado de setembro de 2020 a maio de 2021, com 36 estudantes, por meio de entrevista semiestruturada, utilizando como recurso tecnológico o aplicativo WhatsApp®. Os achados foram analisados à luz da técnica de Análise de Conteúdo de Bardin e discutidos com a literatura científica sobre a temática. Resultados: A necessidade de complementação e aperfeiçoamento na formação em saúde mental acontece devido a disciplina ter pouca carga horária, conteúdos superficiais e poucas atividades práticas nos serviços de saúde mental. A busca também se dá pela afinidade com a área e o desejo de especializar para trabalhar no campo da saúde mental. As estratégias mais utilizadas são ligas acadêmicas, projetos de extensão, iniciação científica e participação em grupos de estudos. Considerações Finais: Embora configurem espaços de protagonismo para os estudantes, a busca por atividades complementares revela a fragilidade da formação nas disciplinas e que essa estratégia é escolhida apenas pelos estudantes que possuem afinidade com o campo de atuação. Descritores: Educação em Enfermagem. Educação Superior. Ensino. Saúde Mental. Enfermagem Psiquiátrica.

Objective: To describe the paths taken byfuture nurse in the search for supplementary training in mental health. Methods: Adescriptive-exploratory study with a qualitative approach, conducted with 36students between September2020 to May2021 through a semi-structuredinterview and using WhatsApp® as technological resource. The findings were analyzed in the light of Bardin's Content Analysis technique and discussed against the scientific literature onthe theme.Results: The need to complement and improve training in mental health is due to the limited hour load of the academic discipline, to superficial contents, and to few practical activities in the mental health services. The search is also the result of affinitywith the area and of the wish to undergo the specialization to work in the field of mental health. The most used strategies are academic leagues, extension projects, scientific initiation and participation in study groups.Final Considerations: Although they represent spaces of protagonism for the students, the search for supplementary activities reveals the fragility of the training in the academic disciplines and that this strategy is only chosen by the students who have an affinity with the field. Descriptors: Nursing Education. Education, Higher. Teaching. Mental Health. Psychiatric Nursing.

Comprehensive Assessment of the Universal Healthcare System in Dentistry Japan: A Retrospective Observational Study.

Japan's universal healthcare insurance is facing economic challenges due to the advanced aging society, however, objective data of dental expenditure has never been introduced. This study aimed to identify the associated factors with dental expenditures using government-provided digitized insurance claims data and calculated the spending in the context of dental cost per person (DCPP). Seven associated factors analyzed were age, demographic, geographic, socioeconomic, regional wealth, the impact of the 8020-national campaign implementation (keep 20 teeth at age 80), and the effect of the home-visit dentistry for the elders. The average DCPP was high in older populations (75+) in all prefectures. The prefectures with the highest and lowest DCPP were significant compared to other states and retained their respective places in the cost hierarchy over the four years. The prefectures with more citizens participating in government assistance programs (GAP) had greater DCPPs. Dental costs were significantly related to geographic regions, age, per capita income, government assistance program prevalence, office complete denture frequency, and home visit care per patient. With a growing aging population, dental care costs will continue to increase, burdening its fiscal future. Associated factors identified should be considered to control the contentious increase of healthcare cost.

Diagnosis of Tooth Prognosis Using Artificial Intelligence.

The accurate diagnosis of individual tooth prognosis has to be determined comprehensively in consideration of the broader treatment plan. The objective of this study was to establish an effective artificial intelligence (AI)-based module for an accurate tooth prognosis decision based on the Harvard School of Dental Medicine (HSDM) comprehensive treatment planning curriculum (CTPC). The tooth prognosis of 2359 teeth from 94 cases was evaluated with 1 to 5 levels (1-Hopeless, 5-Good condition for long term) by two groups (Model-A with 16, and Model-B with 13 examiners) based on 17 clinical determining factors selected from the HSDM-CTPC. Three AI machine-learning methods including gradient boosting classifier, decision tree classifier, and random forest classifier were used to create an algorithm. These three methods were evaluated against the gold standard data determined by consensus of three experienced prosthodontists, and their accuracy was analyzed. The decision tree classifier indicated the highest accuracy at 0.8413 (Model-A) and 0.7523 (Model-B). Accuracy with the gradient boosting classifier and the random forest classifier was 0.6896, 0.6687, and 0.8413, 0.7523, respectively. Overall, the decision tree classifier had the best accuracy among the three methods. The study contributes to the implementation of AI in the decision-making process of tooth prognosis in consideration of the treatment plan.

Current Implementation of Digital Dentistry for Removable Prosthodontics in US Dental Schools.

Objectives: Although digital technology has been widely integrated into dental education, there is limited literature investigating the extent of the integration of computer-aided design and computer-aided manufacturing (CAD-CAM) for removable systems in the dental curriculum. The purpose of this study was to assess the current implementation of CAD-CAM complete and partial dentures in predoctoral (PP) and advanced graduate prosthodontic (AGP) education in US dental schools. The study also aimed to identify potential barriers to its implementation in the dental curriculum. Methods: An online survey with 15 questions was created using online survey software. The survey was distributed to the directors of predoctoral prosthodontics in 56 schools and advanced graduate programs of prosthodontics in 52 schools listed in the 2018-19 American Dental Education Association (ADEA) Directory. Results: The percentage of programs (PP and AGP) implementing CAD-CAM complete dentures (CAD-CAM CDs) and CAD-CAM removable partial dentures (CAD-CAM RPDs) in their didactic, preclinical, and clinical curricula was recorded. CAD-CAM CDs are taught in didactic courses in 54.2% of PP and 65.2% of AGP. However, CAD-CAM RPDs are only taught in 37.5% of PP and 47.8% of AGP. Programs are largely limited by a lack of funds, resources, time, and faculty members. Conclusion: While digital technologies have indeed become more prevalent in dental education, many institutions face barriers to implementation. More research must be conducted in order to support the continued incorporation of digital technologies into dental education.

A cross-sectional survey of patient's perception and knowledge of dental implants in Japan.

BACKGROUND: This study aimed to collect data regarding patient perception and knowledge of dental implants. It was conducted with the hope that the data would provide dental professionals and policymakers with a better understanding of ways to promote implant therapy. METHODS: An anonymous online survey with 10 questions was distributed through 12 dental offices in Tokyo and provincial cities in Japan to assess patient perception and knowledge of dental implants. Harvard Medical School's IRB approved this study. RESULTS: We collected data from 1172 patients (59% female, 41% male). The most common perceptions of implant therapy were that it was "expensive," "advanced," and "scary". Patients' implant knowledge came primarily from magazines or books, while professional dental societies/associations were the least sought out source of information. Patients believed that the purpose of dental implants was to avoid dentures and improve chewing function. Their primary concerns about dental implants were the cost and longevity. Approximately 12% of patients with dental implants and 61% of patients without implants did not know that bone grafts may be required and that sedation during surgery was an option. For patients who experienced sedation during the procedure, 60% of them want it for future surgeries. Patients also had limited knowledge of bone-graft materials and the effects of CBCT radiation; 75% of the patients expressed concerns over the safety of graft materials and radiation exposure. For patients with a history of dental implant therapy, 80% of them would recommend dental implants to their family and friends. CONCLUSIONS: Overall, patients' experiences with dental implant therapy were positive, but there was a lack of patient education regarding dental implants and their associated procedures. Dental professionals need to take the initiative to improve patient education.

Cognitive impairment and edentulism among older adults: an observational study using claims data.

BACKGROUND: The scientific link between mastication strength and cognitive function has not yet been strongly corroborated in population studies. Utilizing large-scale claims, we aim to investigate the association between edentulism and cognitive impairment in older American adults. METHODS: Using de-identified claims from a commercial insurer from 2015-2019, we conducted a retrospective cohort study using multilevel regression models to evaluate the association between denture status and clinically diagnosed cognitive impairment. Secondary analysis included symptomatic cognitive impairment in the outcome. RESULTS: Adjusting for individual-level risk factors, denture status was significantly associated with clinical cognitive impairment with odds ratios of 1.13 (95%CI: 1.02-1.25) and 1.26, (95%CI: 1.09-1.45) for complete dentures on one or both jaws, respectively. Including symptomatic cognitive impairment in the analysis did not substantially change our fundamental findings. CONCLUSION: Prevention and treatment of oral diseases should be considered a key component in preserving the overall wellness of older adults.

Accuracy of a Method to Monitor Root Position Using a 3D Digital Crown/Root Model during Orthodontic Treatments.

This study aimed to assess the accuracy of a method of predicting post-movement root position during orthodontic treatment using a 3D digital crown/root model (3DCRM) created with pre-movement records of both cone-beam computed tomography (CBCT) and dental arch digital scans. Pre- and post-movement CBCT scans and dental arch digital scans of five patients who had completed orthodontic treatments were used in this study. The 3DCRM was superimposed onto the post-movement scanned dental arch to identify the post-movement root position (test method). Post-movement CBCT (referenced as the current method) served as the control to identify the actual post-movement root position. 3D-coordinate analysis revealed no significant differences between the test and current methods along the X and Y axes. However, the discrepancy on the Z axis (especially in cases of intrusion) was greater than that in all other directions for all three tooth types examined (p < 0.05). A strong positive correlation between the degree of discrepancy and the distance of tooth movement was observed on the Z axis (r = 0.71). The 3DCRM method showed promising potential to accurately predict root position during orthodontic treatments without the need for a second CBCT. However, root resorption, which affected the Z axis prediction, needs to be closely monitored using periapical radiographs to complement this method.

Importance of bitewing radiographs for the early detection of interproximal carious lesions and the impact on healthcare expenditure in Japan.

BACKGROUND: Globally, the direct cost of dental caries is approximately $298B yearly, consuming 5-10% of national healthcare budgets. Bitewing radiographs (BWR) are the standard method of diagnosing interproximal dental caries. In Japan, bitewing radiographs are rarely used. This retrospective observational study was conducted to measure the potential economic impact of carious lesions left undiagnosed and untreated due to this omission of bitewing radiographs. METHODS: The total number of existing carious lesions, the number of undiagnosed lesions, and costs of treating these lesions were calculated from the national database of Ministry of Health, Labor and Wellness in Japan between June 2013 and 2017. The number of affected teeth was estimated using prevalence data and undiagnosed lesions were estimated. The expense associated with treating progressed lesions was calculated using the standard Japanese fee structure. BWR trends were assessed, and analyses were performed to understand the differences between states and populations over time. RESULTS: The average number of BWR taken monthly per office was 48.3±1.1 (average ± SD). It was calculated that an average of 6,429,155 lesions went undiagnosed per month, 93.5 teeth per practice, and 1.6 teeth per patient. The cost of treating lesions that went undiagnosed and then progressed into more invasive restorations was estimated to be between $57M-$218M more (difference between NaF varnish and class II restorations), and $150M-$443M more (difference between Class II restoration and crown or crown with RCT). CONCLUSIONS: BWRs are crucial in diagnosing a significant number of carious lesions. There is considerable impact on health and cost to the national health system due to undiagnosed lesions. Practitioners need to be educated on reading and understanding BWR, and policy should be changed to cover BWR.

Gut microbiota and physical exercise in obesity and diabetes - A systematic review.

BACKGROUND AND AIM: The gut microbiota (GM) plays an essential role in maintaining health, and imbalance in its composition is associated with the physiopathogenesis of metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). Diet and antibiotics are known modulators of GM, but the influence of physical exercise in modulating the diversity and abundance of hindgut bacteria is still poorly understood. The aim of this systematic review was to investigate the scientific evidence about the effect of physical exercise on GM modulation in subjects with obesity and T2DM. METHODS AND RESULTS: A search in PubMed, Web of Science, Scopus, Cochrane and Embase databases using keywords related to gut microbiota, physical exercise and metabolic diseases was performed. Eight clinical studies met the inclusion criteria, six in subjects with obesity and two in individuals with T2DM. In three studies carried out in individuals with obesity, exercise was able to positively modulate the diversity of GM and the abundance of some species of bacteria, mostly by increasing the Bifidobacteriaceae family, and the Bacteroides and Akkermansia genera, and by decreasing the Proteobacteria phylum. The studies in subjects with T2DM found that physical exercise may reduce metabolic endotoxemia markers. CONCLUSIONS: Physical exercise may be a beneficial modulation strategy of GM composition in metabolic diseases, specifically aerobic exercises carried out for at least 6 weeks with moderate or high intensity. Nevertheless, well-designed clinical trials are needed to clarify the role of physical exercise on GM in subjects with obesity and T2DM.